Premium
Suppression of adjuvant arthritis of rats by a novel matrix metalloproteinase‐inhibitor
Author(s) -
Hamada Tetsuo,
Arima Nobuyuki,
Shindo Miki,
Sugama Kazushige,
Sasaguri Yasuyuki
Publication year - 2000
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1038/sj.bjp.0703751
Subject(s) - pyridinoline , deoxypyridinoline , inflammation , matrix metalloproteinase , arthritis , endocrinology , rheumatoid arthritis , medicine , cartilage , chemistry , adjuvant , cellular infiltration , infiltration (hvac) , pharmacology , biochemistry , anatomy , enzyme , alkaline phosphatase , physics , osteocalcin , thermodynamics
BAY 12‐9566 (4‐[4‐(chlorophenyl)phenyl]‐4‐oxo‐2S‐(phenylthiomethyl) butanoic acid) is a newly developed, synthetic matrix metalloproteinase (MMP) inhibitor (MMPI) that selectively inhibits MMP‐2, MMP‐3 and MMP‐9 isozymes. We study the effect of BAY 12‐9566 on inflammation and cartilage destruction in adjuvant‐induced arthritis (AA) in rats. Rats were injected with adjuvant and treated for 21 days with vehicle, Indomethacin or BAY 12‐9566. AA was assessed: by measuring arthritic index, paw volume, urinary pyridinoline (Pyr) and deoxypyridinoline (Dpyr); by examining joint inflammation; and by microscopic morphometry of articular cartilages. Oral treatment of rats for 22 days with 50 mg kg −1 body weight/d BAY 12‐9566 showed decreased AA as determined by improvement in body weight gain ( P <0.01), arthritic index ( P <0.05) and swelling of paws contralateral to the adjuvant injection site ( P <0.05). Neutrophil infiltration and collagen degradation were also significantly lower ( P <0.01) in this treatment group. Cartilage destruction was successfully suppressed ( P <0.01) in rats treated with either 50 mg kg −1 body weight/d BAY 12‐9566 or 1 mg kg −1 body weight/d Indomethacin. These results indicate that BAY 12‐9566 successfully suppressed inflammation and cartilage destruction in rats with AA. Moreover, these results also suggested that MMP‐2, MMP‐3 and MMP‐9 are involved in arthritic diseases such as rheumatoid arthritis.British Journal of Pharmacology (2000) 131 , 1513–1520; doi: 10.1038/sj.bjp.0703751